Contamination

Definition
 The presence of unwanted items in our products
Types of contaminants
 Biological
 Chemical
 Physical
Contaminated Products
 Most people at one time or another have come across obvious signs of
contaminated product in things they have bought
Contamination - Pharmaceutical Products
 With pharmaceutical products, contamination is less obvious & we do not always
see the effects the contaminants have on the person using the product
Microbiological Contamination
Micro-organisms.
 Living organisms to small to be seen with the naked eye.
 Bacteria.
 Fungi.
 Protozoans.
 Algae.
 Viruses.
Microbial Growth
 Multiply by binary Fision.
 Require Basic nutrients for growth eg. sugars, proteins, starches, vitamins etc.
 Aerobic / Anaerobic.
 Environmental Determinants - PH & Temperature.
 Cultured in Solid / Liquid media. eg. Agar
Definition of “Sterile”.
 Free of any living organisms.
Particulate Contamination
Chemical Contamination
Product Cross-contamination
 Cross -contamination occurs when any material from one product mixes with
materials of another product
Contamination Control
Causes of Contamination
What are the Dangers ?
 Product Residue
 Conducive Temperature
 Moisture
 Inadequate Cleaning
 Poor Handling
 Contaminated Product
 Unsanitary Connections
Processing.
 Precautions to minimise contamination should be taken during all processing
stages including the stages before sterilisation.
Sources of Microbial Contamination
 Raw Materials - ( including water ).
 Equipment.
 The Atmosphere.
 People.
 Product Containers.
Raw Materials
 Water
 Materials of natural origin
 Packaging / Handling
 Storage
 Quality – Pretesting
 Specifications
 Approval for use
Equipment
 Instruments
 Tanks
 Pumps
 Pipe -work
 Sterilisation
 Calibration
 Cleaning
Atmosphere
 Clean-room
 Change –room
 Biological Safety Cabinet
 Hepa - filters
 Cleaning
 Decontamination
 Monitoring
Environmental Monitoring
 Air
- Settle Plates
- Air Sampler
- Particle Counter
 Surfaces
- Swabs
- Contact Plates
 People
- Hand Plates
- Contact Plates
 Equipment
- Swabs
- Contact Plates
- Bio-burden Samples
Recommended limits for Microbiological Monitoring of Clean Areas in Operation.
People
 Hygiene
 Aseptic Technique
 Knowledge
 Skill
 Clean-room Garments
 Attitude
 Detail to Attention
 Ability to follow established procedures
Product Containers
 Container type
 Sterilisation
 Sealing mechanism
 Stability
 Suitability
 Labelling
 Compatibility
Sanitation.
 The sanitation of clean areas is particularly important.
 They should be cleaned according to a written programme.
 More than one type of disinfectant should be employed.
 Monitoring should check efficacy of cleaning.
Risk Analysis – FMEA
Reducing Risk Severity Factor:
 “Process changes or product redesign…” including “development of an
aseptically produced product into one with terminal sterilization.”
Reducing Probability of Occurrence of Risk:
 “Process automation projects, tighter controls upstream in the process, and new
technologies such as isolators”
Probability of Detecting Failures:
 Validation is “intensified monitoring which should detect flaws or weaknesses,
which may not be normally observable. A media fill is a good example of a validation
test.”
Risk-Based Approach
Critical Control Points
 Causes of Contamination
– Where are the potential routes of contamination in an aseptic process?
 Detection of Contamination Problem
– What measurements are most valuable in indicating sterility assurance?
 Focus on issues of concern
– Influential factors that determine control of the facility and process
– Failure to meet CGMP can impact safety or efficacy

D= Design
 M= Maintenance
Risk-Based Approach
Design
Aseptic Processing requires “A strict design regime, not only on the process area,
but on the interactions with surrounding areas and the movement of people, materials and
equipment so as not to compromise the aseptic conditions.”
 “Continued vigilance throughout the entire manufacturing process”
 “Unstable situations are, in most cases, caused by the influence of arms and
hands.”
Environment
 Studies have shown that “the level of airborne microorganisms in the filling
environment has a profound effect on the level of product contamination.”
 Researchers found a “definable direct relationship between the fraction of product
contaminated and the level of microorganisms in the air surrounding the machine”
Environmental Data and State of Line Qualification
 “It also may be necessary to requalify with acceptable process simulation tests in
response to adverse trends or failures in the ongoing monitoring of the facility or process
such as: Continued critical area EM results above action/alert limits…”
“Facility and equipment modification, significant changes in personnel, anomalies
in environmental testing results and end product sterility testing showing contaminated
products may all be cause for revalidating the system.”
Design, Environment, & Personnel: Link to Sterility
 Widely accepted that each of the following is crucial to assuring sterility:
Design
Environment
Personnel
 That’s theory, what about actual experiences?
 The above principle plays out in the many case studies we see throughout each
year.
 Lack of adherence to CGMP in these areas underlies the vast number of failures
in the industry.
Sources of Contamination:
Investigation Conclusions (e.g.)
 Aseptic practices:
 Personnel returned after long winter shutdown
 Operator reached over open vials to remove fallen vial on line with gloved hands
 Poor personnel flow
 Poor aseptic connections
 Poor Sanitization: Procedures deficient, or poorly executed
 Construction in another room on the same floor caused increased airborne
contamination (sporeforming bacteria) in facility
 Poor gown design: Introduced new gown component, but then found it was
contamination source

Why is Contamination Control so important?

 GMP/Legal Requirement
All Regulatory guidelines on GMP have sections dedicated to Contamination
Control
Maintaining Equipment
Poorly maintained equipment can lead to product and material contamination
eg: Rust on equipment surfaces close to product contact points is a major source of
contamination.
Utilising only approved Materials
Ensure all the materials arriving to the work centre are appropriate, clean and their
containers/boxes have not been damaged.
Anything that has been clearly damaged or tampered must not be used.